Novel Pt-loaded layered double hydroxide nanoparticles for efficient and cancer-cell specific delivery of a cisplatin prodrug

Abstract

Providing strategies to overcome the toxicity and side effects of platinum-based antineoplastic drugs is crucial for their future development. Here we describe a strategy of using low-cytotoxic and non-functionalized layered double hydroxide (LDH) nanoparticles (NPs) to increase the cancer-cell specificity as well as anticancer efficacy of a cisplatin prodrug. In our study, the prodrug is efficiently loaded into and protected by LDH. The Pt-loaded NPs exhibit much higher cytotoxicity than the prodrug against cancer cells. Moreover, the Pt-loaded NPs are much less active against certain types of normal cells. We further investigate the mechanisms behind these phenomena including cellular uptake, cell cycle arrest, and apoptosis induction. We find that LDH is able to significantly improve both the cellular uptake of Pt and genomic DNA platination in cancer cells, and the Pt-loaded NPs induce severe apoptosis in cancer but not normal cells. All of these findings imply that Pt-loaded LDH NPs have great potential to be further developed as anticancer nanomedicine.